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Pyridine → 5-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-7-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester

HRID 2353964
ノート
印刷プレビュー

反応式

HRID 2353964 の反応式
[C:1](Cl)(=[O:3])[CH3:2].N1C=CC=CC=1.[C:11]([O:15][C:16]([N:18]1[CH2:24][CH2:23][CH2:22][CH:21]([NH:25][CH2:26][C:27]2[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[C:29]([C:37]([F:40])([F:39])[F:38])[CH:28]=2)[C:20]2[CH:41]=[C:42]([C:45]([F:48])([F:47])[F:46])[CH:43]=[CH:44][C:19]1=2)=[O:17])([CH3:14])([CH3:13])[CH3:12]>ClCCl>[C:11]([O:15][C:16]([N:18]1[CH2:24][CH2:23][CH2:22][CH:21]([N:25]([C:1](=[O:3])[CH3:2])[CH2:26][C:27]2[CH:28]=[C:29]([C:37]([F:40])([F:38])[F:39])[CH:30]=[C:31]([C:33]([F:36])([F:34])[F:35])[CH:32]=2)[C:20]2[CH:41]=[C:42]([C:45]([F:48])([F:46])[F:47])[CH:43]=[CH:44][C:19]1=2)=[O:17])([CH3:14])([CH3:12])[CH3:13]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 86616081(+/-)-t-Butyl-5-(3,5-bistrifluoromethylbenzylamino)-7-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

生成物 1

HCID 590030995-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-7-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester収率 83%

試薬・触媒・溶媒 1

HCID 6344
Dichloromethane
溶媒

実験手順

Add 3,5-bis(trifluoromethyl)benzylamine (0.1 g, 0.4 mmol) followed by titanium isopropoxide (1.0 mL) to 5-Oxo-7-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester (0.13 g, 0.4 mmol) and stir at room temperature overnight. Dilute the mixture with 5 mL of Methanol and add sodium borohydride (0.8 mmol). Stir the suspension at room temperature for 30 min then dilute with water (20 mL) and ethyl acetate (20 mL). Filter the resulting emulsion through celite and wash with ethyl acetate (3×20 mL). Separate the organics, dry over sodium sulfate, and filter. Remove the solvent under vacuum to afford (+/−)-t-butyl-5-(3,5-bistrifluoromethylbenzylamino)-7-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate crude (0.2 g, MS (ES+): 557 (M+H)). Without further purification, add acetyl chloride (0.8 mmol) and pyridine (0.8 mmol) to a solution of (+/−)-t-butyl-5-(3,5-bistrifluoromethylbenzylamino)-7-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate in dichloromethane. After stirring for 2 h remove solvent under vacuum and chromatograph over silica gel using ethyl acetate/hexane (5-40%) to elute. This affords the title compound as an oil (0.2 g, 83%) which foams under vacuum: MS (ES−): 597 (M−H).

後処理

  1. customWithout further purification
  2. customremove solvent under vacuum and chromatograph over silica gel
  3. washto elute

出典と根拠

ORDレコード
ord-7a5596f6073049ceac253bd3a6c572cd
出典データセット
uspto-grants-2010_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07749992B2

反応ノート

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